Neuropathic pain
induced by nervous system damage affects increasing number of patients and
significantly decreases the quality of their life. Conventional analgesics,
especially opioids, have poor efficiency and produce a plethora of undesired
side effects. Therefore, it is important to find a new, effective and long-term
therapy suitable for patients suffering from neuropathic pain.

Fig. 1 The influence of maraviroc (M) on neuroimmunological changes in spinal cord and DRG under neuropathic pain

Recent studies
suggest that interactions between neurons, glia and immune cells, mediated by
proinflammatory factors such as cytokines, play a crucial role in neuropathic
pain development. Furthermore, recent evidence suggest that chemokines are imperative
in mediating neuropathic pain. Previous studies point to the involvement of CC
chemokine ligand 5 (CCL5) in neuropathic pain development and maintenance.
Thus, we were focused on investigating the influence of repeated administration of selective CC
chemokine receptor 5 (CCR5) antagonist, namely maraviroc, on neuropathic
pain-related behaviors, opioid effectiveness and associated biochemical changes
in neuropathy. Maraviroc is an antiretroviral drug approved by the Food and
Drug Administration for HIV infection treatment. In our experiments we used
chronic constriction injury (CCI) model of neuropathic pain in rats. Maraviroc
was administered intrathecally twice before CCI operation, and then once a day over
next 7 days. Our results [1] demonstrated
that pretreatment and repeated injections of maraviroc attenuate neuropathic
pain symptoms 7 days after sciatic nerve injury in rats. Biochemical analysis
revealed that maraviroc prevents the activation of microglia and astrocytes in
central nervous system induced by sciatic nerve injury.

Our in vitro
studies showed that these cells, once activated, are the main source of
pronociceptive chemokines. We also demonstrated that the levels of CCL3, CCL4,
CCL5 and CCL7 are increased in the spinal cord and dorsal root ganglia (DRG)
after the nerve injury. Interestingly, maraviroc effectively diminished
CCI-elevated levels of CCL3, CCL4 and CCL5 in the spinal cord and the level of
CCL5 in DRG (Fig. 1). Furthermore, our behavioral
experiments provided new evidence that maraviroc not only attenuates the development
of neuropathic pain symptoms but also enhances the analgesic properties of
morphine and buprenorphine. Thus, we hypothesize that CCR5 chemokine receptor
might be an interesting target for creating a new therapy for patients
suffering from neuropathic pain, which may exert beneficial influence on effectiveness
of conventional opioid analgesics.

Acknowledgments:Supported by the National Science Centre, Poland grant
OPUS NCN2011/03/B/NZ4/00042 and statutory funds of the Institute of
Pharmacology, Polish Academy of Sciences. Jurga A., Slusarczyk J. and Trojan E.
are Ph.D. students funded by KNOW scholarship sponsored by the Ministry of
Science and Higher Education, Poland.